Unravelling advanced glycation end products as emerging therapeutic targets in diabetic retinopathy management

Diabetes mellitus, characterized by chronic hyperglycemia, is a rapidly growing global health concern with an anticipated prevalence of 700 million by 2045. Diabetic retinopathy (DR), a major complication, is the leading cause of vision loss in working-age adults worldwide. Neurovascular units (NVUs), comprising neurons, glial cells, and vessels, maintain retinal homeostasis, and their impairment is considered a primary pathological change in early DR. While glycemic control is conventionally assessed by hemoglobin A1c (HbA1c), studies suggest additional factors influencing DR risk beyond equivalent HbA1c levels. Chronic hyperglycemia triggers neurovascular impairment through advanced glycation end-products (AGEs), inflammation, and oxidative stress. AGEs, accumulating irreversibly, play a crucial role in DR and other diabetic complications. Therapeutic interventions targeting AGEs, both endogenous and exogenous, are gaining traction, offering potential avenues to preserve NVU function. Existing drugs such as pioglitazone, angiotensin II receptor blockers, ACE inhibitors, calcium channel blockers, and statins, along with natural compounds like benfotiamine and cinnamon bark extract, show promise as anti-AGE strategies. This multifaceted approach presents a paradigm shift in early diabetic retinopathy treatment, with ongoing research focusing on refining these strategies for improved management.